In vitro human Th-cell responses to a recombinant hepatitis C virus antigen: Failure in IL-2 production despite proliferation

Hepatitis C Virus (HCV) causes chronic infection in 80-90% of those exposed and persists despite evidence of immune recognition. To understand the imm unological basis of this phenomenon, we have synthesized a non structural ( NS) protein that is critical to HCV infection and replication, NS3, and use d it to study in vitro helper T-cell responses from infected individuals. S trong proliferative responses were generated by peripheral T-cells isolated from a subset of chronically infected patients, but not by normal, non-inf ected controls. Interestingly, though gamma-interferon (gamma Ifn) and IL-1 0 were both secreted in response to stimulation by NS3 antigen, IL-2 was no t. In contrast, IL-2 was secreted in response to influenza virus vaccine an tigen. Lack of IL-2 induction was confirmed by a failure to amplify IL-2 mR NA upon NS3 antigen stimulation, whereas IL-4, IL-15, and gamma Ifn mRNA we re seen as early as 24 h. The predominance of IL-4 and IL-10 and the lack o f IL-2 suggests that in vitro responses to at least some HCV antigens are b iased towards a Th2 phenotype, which may be conducive to viral persistence. Human Immunology 60, 187-199 (1999). (C) American Society for Histocompati bility and Immunogenetics, 1999. Published by Elsevier Science Inc.